We have discovered a novel mechanism for platelet lysis and clearance in HIV-I-ITP patients, which is complement independent and induced by H202/free radicals. The Ab is directed against an immunodominant platelet GPIIla49-66 epitope and sequestered within serum immune complexes. Other Ab's against GPIIla do not have this effect. A rabbit Ab raised against GPIIla49-66 has the same effect. The mechanism of H202/free radical induction is via an apparent NADPH oxidase pathway in platelets since it is inoperative in NADPH oxidase deficient mice (p47phox(-/-) and gp91phox(-/-)) and dependent upon a functioning platelet 12-1ipoxygenase. I. Analyze the Presence of a Functioning NADPH Oxidase Pathway in Platelets. 2. Analyze the Mechanism of the Requirement of Platelet 12-Lipoxygenase for Ab-induced Platelet fragmentation. 3. Determine whether NADPH oxidase/ROS induced platelet fragmentation is a unique effect of anti- GPIIla49-66 Ab in HIV-I-ITP patients or a general mechanism for other platelet destructive disorders. 4. Determine whether anti-GPIIla49-66 is a result of molecular mimicry with antigen of infectious origin or its products.